血清基质蛋白酶9和胱抑素C水平与脑梗死病变程度的相关性

目的探讨血清基质蛋白酶9(MMP-9)和胱抑素C(Cys-C)水平与脑梗死病变程度的相关性。方法选取本院神经内科收治的首次发病的48 h内的脑梗死患者90例作为观察组,另选取同期行体检的健康者90例作为对照组。检测2组研究对象的血清MMP-9和Cys-C水平,分析二者水平与脑梗死病变程度的关系。结果观察组患者血清MMP-9和Cys-C水平均显著高于对照组(P0.05)。观察组轻、中、重度患者的血清MMP-9和Cys-C水平呈现逐渐升高的状态,差异均有统计学意义(P0.05)。观察组大梗死灶患者的血清MMP-9和Cys-C水平显著高于中、小梗死灶患者(P0.05),中梗死灶患者的血清MMP-9和Cys-C水平显著高于小梗死灶患者(P0.05)。结论血清MMP-9和Cys-C水平与脑梗死的发生、病情严重程度及梗死灶大小均有相关性。     

脑梗死患者血清中MMP-9表达水平的临床意义

目的通过动态分析脑梗死患者血清中基质金属蛋白酶-9（MMP-9）的表达水平,探讨患者血清MMP-9表达水平与脑梗死体积、神经功能缺损程度及预后的关系。方法应用酶联免疫吸附法（ELISA）检测120例脑梗死患者（梗死组）和100例健康者（对照组）的血清MMP-9的表达水平。采用统计学方法分析MMP-9水平与脑梗死的关系。结果梗死组血清MMP-9水平在第1、7、14天均明显高于对照组（P〈0．05）,且血清MMP-9水平与脑梗死体积、神经功能缺损程度及患者的预后明显相关。可认为血清MMP-9高水平是判断脑梗死患者预后的独立危险因素。结论血清MMP-9水平升高是脑梗死的一个危险因素。     

基质金属蛋白酶9和胱抑制素C动态变化在脑梗死中的应用研究

目的通过观察脑梗死患者血清中基质蛋白酶9（MMP-9）和胱抑素C（Cys-C）的含量水平变化与脑梗死患者病变程度的关系,探讨其在脑梗死发展过程中的作用。方法选择首次发病的48h内的急性脑梗死患者83例为研究组。测定患者发病第3、7、14d时的血清MMP-9及Cys-C水平。并与52例健康对照者的检测结果进行比较。结果研究组患者血清MMP-9及Cys-C水平均显著高于对照组（t=11.38,P=0.02;t=13.65,P=0.007）。脑梗死损伤重度组患者血清MMP-9及Cys-C水平均显著高于轻微脑梗死组患者（t=8.93,9.26,2.75,1.98;P=0.008,0.005,0.01,0.04）。大梗死灶组患者血清MMP-9及Cys-C水平显著高于中、小梗死灶组,差异具有统计学意义（P〈0.05）。且入院3d时,中梗死灶组患者MMP-9及Cys-C水平均显著高于小梗死灶组,差异具有统计学意义（P〈0.05）。结论血清MMP-9及Cys-C水平与脑梗死的发生及梗死体积大小、病情严重程度相关。脑梗死早期检测血清MMP-9及Cys-C水平可作为脑梗死的预测因子,是判断脑梗死患者病程转化及近期预后的重要指标。     

颈动脉重度狭窄或闭塞导致的脑梗死患者同型半胱氨酸检测的意义

目的探讨同型半胱氨酸(Hcy)水平与颈动脉颅外段重度狭窄或闭塞导致的脑梗死发生、发展的关系。方法选择75例颈动脉颅外段重度狭窄或闭塞导致的脑梗死患者和对照组40名健康体检者,测定其血浆Hcy水平,分析Hcy水平与脑梗死、脑梗死局部解剖模式、颈动脉不稳定斑块、梗死灶大小及神经功能缺损程度的相关性。结果脑梗死组Hcy水平明显高于对照组;区域梗死Hcy水平明显高于其他4种梗死模式;不稳定斑块组Hcy水平明显高于稳定斑块组;梗死灶体积越大,血浆Hcy水平越高,神经功能缺损程度越重。结论血浆Hcy水平与颈动脉重度狭窄或闭塞导致的脑梗死关系密切,支持特定的梗死模式,是脑梗死病情严重程度的危险因子及预测因子。     

急性脑梗死患者血浆溶血磷脂酸水平检测的临床意义

目的探讨急性脑梗死(ACI)患者血浆溶血磷脂酸(LPA)水平变化及其临床意义。方法测定100例住院ACI患者LPA水平,分析LPA水平变化与其病情严重程度、梗死体积大小及其病情变化的相关性。结果ACI患者血浆LPA含量明显高于对照组(P<0.01),并在发病后24h达到高峰。在ACI患者中大梗死灶、中梗死灶ACI患者组血浆LPA含量明显高于小梗死灶ACI患者(P<0.01),进展性脑卒中组血浆LPA明显高于完全性脑卒中组(P<0.01)。且LPA水平与临床神经功能缺损评分呈正相关(r=0.263,P<0.05)。结论LPA水平与ACI患者病情严重程度及其变化密切相关,LPA可能在ACI的发生发展中起一定作用。     

急性脑梗死患者血清基质金属蛋白酶-9和同型半胱氨酸检测的临床价值

目的通过对急性脑梗死患者血清基质金属蛋白酶-9(MMP-9)和同型半胱氨酸(Hcy)浓度变化的分析,探讨其在脑梗死预测、诊断及预后评估中的临床价值。方法选取临床确诊的62例急性脑梗死的病例作为患者组,40例健康体检者作为健康对照组。分别应用酶联免疫吸附法(ELISA)和循环酶法测定血清MMP-9和Hcy的浓度。根据脑血管病学术会议规定的脑梗死患者临床神经功能缺损程度评分标准(CNFDS)对脑梗死患者于入院时及入院后3周的状态进行评分,且患者均进行CT检查确诊。应用SSPS11.5软件包进行统计学处理。结果急性脑梗死患者血清MMP-9水平明显高于健康对照组(P<0.01),且其水平与梗死灶体积及患者预后有显著相关性。患者组血清Hcy水平明显高于健康对照组,差异有统计学意义(P<0.01)。结论急性脑梗死患者血清MMP-9和Hcy水平明显升高,且MMP-9的增高程度可为中枢神经系统受损程度提供信息,作为预后评估及药物治疗的重要依据。而血清Hcy水平是导致脑动脉粥样硬化的一个独立的危险因素,可作为预测急性脑梗死的依据。     

血浆基质金属蛋白酶-9在预测急性脑梗死溶栓后并发脑出血中的意义

目的研究血浆基质金属蛋白酶-9(MMP-9)对预测急性脑梗死溶栓治疗后并发脑出血的作用。方法 100例急性脑梗死患者随机分成2组,溶栓组60例(A组),给与尿激酶静脉溶栓治疗;非溶栓组40例(B组),仅给与常规治疗。比较2组患者脑出血发生率、各时间点MMP-9水平以及并发脑出血与未并发脑出血患者MMP-9水平。结果溶栓组脑出血发生率(11.7%)高于非溶栓组(2.5%),但无统计学意义。发病后5 d溶栓组血浆MMP-9水平明显低于非溶栓组(P<0.05),其余各时间点两组MMP-9水平均无明显差别。发病后6 h血浆MMP-9水平与梗死面积呈正相关(P<0.01),梗死灶越大MMP-9水平越高。并发出血患者入院时MMP-9水平明显高于未并发出血患者(P<0.05);以入院时MMP-9水平>195μg/L为标准,其后并发出血的发生率差异明显(P<0.01)。结论血浆MMP-9水平>195μg/L可以做为早期(<6 h)预测脑梗死并发脑出血的指标(7例/8例,阳性预测值87.5%;81例/92例,阴性预测值88.0%),对脑梗死溶栓治疗后并发脑出血提前进行预警有重要临床意义。     

血浆基质金属蛋白酶-9与糖耐量低减患者亚临床动脉粥样硬化的相关性研究

目的:探讨糖耐量低减(IGT)患者血浆基质金属蛋白酶-9(MMP-9)与亚临床动脉粥样硬化(AS)的关系。方法:选择IGT患者60例作病例组,糖耐量正常(NGT)者30例作为对照组。比较两组间MMP-9、颈动脉内膜中层厚度(IMT)及各项代谢指标的差异。采用Logistic回归分析IGT患者亚临床AS的独立危险因素。结果:IGT组患者血浆MMP-9、颈动脉IMT、亚临床AS发生率显著高于NGT组(P<0.01);颈动脉平均IMT与血浆MMP-9水平呈正相关(r值为0.75,P<0.01);Logistic回归分析结果发现,MMP-9、餐后2h血糖(2hBG)、高三酰甘油血症是亚临床AS发生的独立危险因素。结论:亚临床AS在IGT患者中有较高的发生率;MMP-9与IGT患者IMT增厚呈高度相关性;MMP-9、2hBG、高三酰甘油血症是IGT患者亚临床AS发生的独立危险因素。     

纹状体内囊梗死患者不良预后危险因素研究

目的:对纹状体内囊梗死患者不良预后的危险因素进行相关性分析。方法:收集分析50例发病48 h内的急性纹状体内囊梗死患者的临床资料。根据起病1个月的改良Rankin评分(m RS评分)将患者分为功能恢复良好组和功能恢复不良组。入组患者加做磁共振弥散张量成像(DTI),结合DTI测量患侧感兴趣区的各向异性分数值(FA值),计算FA值减低的百分比(LFA)。采集的危险因素包括早期运动障碍加重、入院时美国国立卫生院卒中量表(NIHSS)评分、性别、年龄、糖尿病、高血压、入院时随机血糖、入院时升高的收缩压、入院时升高的舒张压、入院时血脂水平、入院时尿酸、梗死灶体积、LFA值。单变量分析影响纹状体内囊梗死患者预后的差异有统计学意义的危险因素作为自变量,代入多变量Logistic回归方程,分析影响纹状体内囊梗死患者预后的独立危险因素。结果:LFA(OR 1.863,CI 1.199~2.864,P=0.006)是预测纹状体内囊梗死患者功能恢复的独立危险因素。结论:LFA可能是纹状体内囊梗死患者不良预后的独立危险因素。     

血管性痴呆患者VILIP-1、MMP-9、ApoE水平变化及危险因素分析

目的探讨血管性痴呆(VD)患者视锥蛋白样蛋白1(VILIP-1)、基质金属蛋白酶-9(MMP-9)、载脂蛋白E(ApoE)的变化及危险因素。方法选取VD患者116例为VD组,无认知功能障碍的脑梗死患者110例为对照组。比较2组患者血清VILIP-1、MMP-9、ApoE水平及简易精神状态量表(MMSE)评分。采用简单线性相关法分析VILIP-1、MMP-9、ApoE水平与MMSE评分的相关性,采用单因素及多因素分析探讨血管性痴呆的危险因素。结果 VD组入院时美国国立卫生研究院卒中量表(NIHSS)评分、脑梗死部位、梗死病灶大小、颈动脉斑块检出率与对照组比较,差异有统计学意义(P0.05)。VD组血清VILIP-1、MMP-9、ApoE水平高于对照组,差异有统计学意义(P0.05)。VD组定向力、注意力和计算力、记忆力、回忆能力、语言能力、MMSE总分高于对照组,差异有统计学意义(P0.05)。VD组的血清VILIP-1、MMP-9、ApoE水平与MMSE总分均呈显著负相关(P0.05)。Logistic回归模型结果显示,血清VILIP-1、MMP-9、ApoE水平增高,入院时NIHSS评分较高,额叶部位脑梗死以及大梗死病灶是脑梗死患者并发VD的独立危险因素(P0.05)。结论血清VILIP-1、MMP-9、ApoE水平升高会增高脑梗死患者并发VD的风险,且与患者认知受损程度有关。     

急性胰腺炎患者血清Toll样受体9和基质金属蛋白酶-9与继发感染及器官功能衰竭的相关性

目的观察急性胰腺炎患者血清Toll样受体9(Toll-like receptor 9,TLR9)、基质金属蛋白酶-9(matrix metallopeptidase-9,MMP-9)水平变化,探讨其预测继发感染、器官功能衰竭的价值。方法72例急性胰腺炎患者,均给予改善微循环、解痉止痛、抑制胰酶分泌、抗感染等规范治疗。治疗7d后,发生继发感染者31例为感染组,未发生继发感染者41例为未感染组;发生器官功能衰竭者8例为衰竭组,未发生器官功能衰竭者64例为未衰竭组。比较感染组与未感染组、衰竭组与未衰竭组一般资料及血清TLR9、MMP-9、白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平;多因素logistic回归分析急性胰腺炎患者发生继发感染及器官功能衰竭的影响因素;绘制ROC曲线评估血清TLR9、MMP-9预测急性胰腺炎患者继发感染及器官功能衰竭发生风险的效能。结果感染组与未感染组,衰竭组与未衰竭组年龄、性别比例及合并糖尿病、高血压、高脂血症比率比较差异均无统计学意义(P>0.05);感染组血清TLR9[(17.30±2.37)μg/L]、MMP-9[(29.42±9.82)μg/L]、TNF-α[(66.40±5.37)μg/L]水平高于未感染组[(14.49±1.71)、(17.02±4.02)、(63.22±1.79)μg/L](P<0.05),血清IL-6[(56.45±4.32)μg/L]水平与未感染组[(57.21±4.29)μg/L]比较差异无统计学意义(P>0.05);衰竭组血清TLR9[(19.23±2.12)μg/L]、MMP-9[(65.56±30.91)μg/L]、IL-6[(59.67±7.60)μg/L]水平高于未衰竭组[(15.07±2.13)、(23.57±18.63)、(54.11±2.11)μg/L](P<0.05),血清TNF-α[(62.35±3.23)μg/L]水平与未衰竭组[(61.95±3.18)μg/L]比较差异无统计学意义(P>0.05)。多因素logistic回归分析结果显示,血清TLR9(OR=1.558,95%CI:1.428~2.727,P<0.001)、MMP-9(OR=1.818,95%CI:1.748~1.895,P<0.001)、TNF-α(OR=1.372,95%CI:1.211~1.979,P<0.001)是急性胰腺炎患者发生继发感染的影响因素;血清TLR9(OR=1.942,95%CI:1.933~3.012,P<0.001)、MMP-9(OR=1.978,95%CI:1.926~3.969,P<0.001)、IL-6(OR=1.950,95%CI:1.929~2.971,P<0.001)是急性胰腺炎患者发生器官功能衰竭的影响因素。ROC曲线分析结果显示,TLR9以18.134μg/L为最佳截断值,预测急性胰腺炎患者继发感染发生风险的AUC为0.806(95%CI:0.700~0.911,P<0.05),灵敏度为87.1%,特异度为97.6%;MMP-9以32.635μg/L为最佳截断值,预测急性胰腺炎患者继发感染发生风险的AUC为0.819(95%CI:0.708~0.929,P<0.05),灵敏度为83.9%,特异度为95.1%;TLR9以20.216μg/L为最佳截断值,预测急性胰腺炎患者器官功能衰竭发生风险的AUC为0.824(95%CI:0.722~0.926,P<0.05),灵敏度为88.0%,特异度为97.9%;MMP-9以70.123μg/L为最佳截断值,预测急性胰腺炎患者器官功能衰竭发生风险的AUC为0.840(95%CI:0.725~0.955,P<0.05),灵敏度为84.0%,特异度为95.7%。结论发生继发感染、器官功能衰竭的急性胰腺炎患者血清TLR9、MMP-9水平升高,TLR9、MMP-9在评估急性胰腺炎患者预后中有较高价值。     

Long-term influence of diet and/or omega-3 fatty acids on matrix metalloproteinase-9 and pregnancy-associated plasma protein-A in men at high risk of coronary heart disease

BACKGROUND: Matrix metalloproteinases (MMPs) are important in the atherosclerotic process. The relationship between MMPs and traditional risk factors for cardiovascular disease (CVD) and any influence of lifestyle changes are largely unknown. OBJECTIVES: In a factorial design, we studied the effects of 3 years of dietary counselling and/or n-3 PUFA supplementation (2.4 g/d) on the levels of MMP-9, tissue inhibitor of metalloproteinase (TIMP-1) and pregnancy-associated plasma protein (PAPP-A) in a population of elderly men at high risk of CVD (n = 563, age 70+/-6 years). We further explored the association between these markers and different disease entities, carotid intima media thickness (IMT) and traditional risk factors for CVD. RESULTS: Smokers had significantly higher levels of MMP-9 (p<0.0001), and TIMP-1 levels were lower in subjects with previous AMI (p = 0.021). MMP-9 was significantly correlated with LDL-C and inversely with HDL-C (both p<0.0001). There were no significant correlations between the measured variables and IMT. Significant reductions in MMP-9 and PAPP-A levels after 36 months were found in all study groups, however, with no between-group differences. CONCLUSIONS: The elevated levels of MMP-9 in smokers and the reduced levels of TIMP-1 in patients with previous AMI reflect an importance of MMPs in the development of CVD. Intervention with diet and/or n-3 PUFA supplementation did not influence the levels of MMP-9, TIMP-1 or PAPP-A in the present population.     

Serum metalloproteinase 9 levels in patients with coronary artery disease: a novel marker of inflammation.

BACKGROUND: The finding that expression of metalloproteinases (MMPs) is induced in atherosclerotic plaques prone to rupture suggests the possibility that patients with atherosclerotic diseases would show enhanced blood levels of MMPs and that MMPs might represent a potential inflammatory risk factor for atherosclerosis. Therefore, the present study was aimed at verifying whether MMPs may represent sensitive markers of inflammation in patients with coronary artery disease. METHODS: MMP-2, MMP-9, interleukin (IL)-6, C-reactive protein (CRP), and fibrinogen levels were measured in blood samples obtained from 66 cases with previous acute myocardial infarction and 66 control subjects similar for age, sex, and major atherosclerotic risk factors but without history or evidence of atherothrombotic diseases. RESULTS: Biohumoral markers of inflammation and MMP-9 levels were significantly elevated in cases compared with controls (median values 40.6 versus 9.8 ng/mL; p < .0001), whereas MMP-2 levels did not differ between the two groups (median values 839 versus 873 ng/mL; p = .53). A direct correlation was found among MMP-9, CRP, IL-6, and fibrinogen levels. Conditional logistic regression analysis showed that MMP-9 is related to myocardial infarction (p = .006) even after adjusting for cardiovascular medications and CRP. CONCLUSION: These findings suggest that measurement of serum MMP-9 levels may represent a novel marker of inflammation in patients with known coronary artery disease and might provide an index of plaque activity in this clinical setting.     

MMP-2、MMP-9在肺癌中的表达及其与肺癌转移和预后关系的研究

目的:探讨非小细胞肺癌(NSCLC)组织中基质金属蛋白酶-2(MMP-2)及基质金属蛋白酶-9(MMP-9)的表达水平与肺癌转移和预后的关系。方法:应用免疫组化(LSAB法)检测了108例非小细胞肺癌和19例肺良性病变中MMP-2、MMP-9的表达水平。结果:(1)肺癌组织中MMP-2、MMP-9的表达水平均显著高于癌旁肺组织和肺良性病变肺组织(P<0.01)。(2)伴有淋巴结或/和远外转移的肺癌中MMP-2、MMP-9的表达水平均显著高于不伴有淋巴结或/和远外转移的肺癌(P<0.01或P<0.05)。(3)MMP-2、MMP-9在肺鳞癌中的表达水平显著高于在腺癌和腺鳞癌中的表达水平(P<0.01)。(4)肺癌组织中MMP-2、MMP-9的表达水平呈显著正相关(P<0.05)。(5)多因素COX比例风险模型分析显示:MMP-2、MMP-9的表达水平对于预测肺癌预后具有一定意义。结论:(1)肺癌中MMP-2、MMP-9的表达水平明显升高,且与肺癌的进展和转移有密切关系。(2)肺癌组织中MMP-2、MMP-9的表达水平呈显著正相关(P<0.05)。(3)检测肺癌中MMP-2、MMP-9的表达水平有助于预测肺癌的预后,指导肺癌的多学科综合治疗。     

Gelatinase matrix metalloproteinase (MMP)-2 and MMP-9 of the umbilical cord blood in preeclampsia.

BACKGROUND: Preeclampsia is associated with accumulation of collagen and proteoglycans in the umbilical cord tissues as a result of increased biosynthesis and decreased degradation of these components. Matrix metalloproteinases (MMPs) are enzymes engaged in the degradation of collagen and the protein core structures of proteoglycans, including those which bind peptide growth factors. METHODS: We used Western immunoblots, immunoenzymatic assay (ELISA) and zymography techniques for the detection of gelatinases and their inhibitors. RESULTS: We found that both umbilical cord blood plasma and serum of controls and preeclamptic newborns contained MMP-2 and MMP-9, as well tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2. The umbilical cord plasma of preeclamptic subjects contained large amounts of MMP-9 in a form of complexes with other plasma components, and zymographic analysis demonstrated increased gelatinolytic activity at a position corresponding to MMP-9, compared to control samples. By contrast, MMP-2, TIMP-1 and TIMP-2 data showed no significant differences between preeclamptic and control samples. CONCLUSIONS: The high activity of MMP-9 in preeclamptic plasma suggests its participation in the proteolytic release of peptide growth factors from their complexes with other matrix components, with subsequent stimulation of cell division and matrix biosynthesis. We suggest this might represent one of the mechanisms for matrix remodeling in the umbilical cord of preeclamptic newborns.     

Independent association of matrix metalloproteinase-10, cardiovascular risk factors and subclinical atherosclerosis

OBJECTIVES: Circulating levels of matrix metalloproteinase (MMP)-10 are related to inflammation in asymptomatic subjects with cardiovascular risk factors. Whether MMP-10 is associated with the severity of atherosclerosis remains to be determined. This study examines the relationship of systemic MMP-10 levels with atherosclerotic risk factors and subclinical atherosclerosis. METHODS AND RESULTS: Circulating levels of MMP-1, -9 and -10, and markers of inflammation [fibrinogen, interleukin-6, von Willebrand factor, and high-sensitivity C-reactive protein (hs-CRP)] were measured in 400 subjects (mean age 54.3 years, 77.7% men) with cardiovascular risk factors but free from clinical cardiovascular disease. Subclinical atherosclerosis was evaluated by both the mean carotid intima-media thickness (IMT) and the presence of atherosclerotic plaques with the use of B-mode ultrasound in all subjects. MMP-10 levels were positively correlated with fibrinogen (r = 0.24, P < 0.001), hs-CRP (r = 0.14, P < 0.01) and carotid IMT (r = 0.17, P < 0.01). The association between MMP-10 and IMT remained significant in multiple regression analysis (P < 0.02) when controlling for traditional atherosclerotic risk factors and inflammatory markers. Such an association was not observed for MMP-1 and -9. Subjects in the highest MMP-10 tertile had significantly higher carotid IMT (adjusted odds ratio 6.3, 95% confidence interval 1.3-31.4, P = 0.024). In addition, MMP-10 levels were significantly higher in patients with carotid plaques (n = 78) than in those with no plaques after adjusting for age and sex (P < 0.01). CONCLUSION: Higher serum MMP-10 levels were associated with inflammatory markers, increased carotid IMT and atherosclerotic plaques in asymptomatic subjects. Circulating MMP-10 may be useful to identify subclinical atherosclerosis in subjects free from cardiovascular disease.     

Inverse relationship between markers of nitric oxide formation and plasma matrix metalloproteinase-9 levels in healthy volunteers

BACKGROUND: Nitric oxide (NO) is a major regulator of cardiovascular homeostasis and has anti-atherogenic properties. Reduced NO formation is associated with endothelial dysfunction and with cardiovascular risk factors. Although NO downregulates the expression and activity of the pro-atherogenic enzyme matrix metalloproteinase-9 (MMP-9), no previous clinical study has examined whether endogenous NO formation is inversely associated with the circulating levels of pro-MMP-9, which are associated with cardiovascular events. We examined this hypothesis in 175 healthy male subjects who were non-smokers. METHODS: To assess NO bioavailability, the plasma concentrations of nitrite, nitrate, and cGMP were determined using an ozone-based chemiluminescence assay and an enzyme immunoassay. Pro-MMP-9 and pro-MMP-2 levels were measured in plasma samples by gelatin zymography. RESULTS: We found significant negative correlations between pro-MMP-9 levels and plasma nitrite (P=0.035, rs= -0.159), nitrate (P=0.040, rs= -0.158), and cGMP (P=0.011, rs= -0.189) concentrations. However, no significant correlations were found between pro-MMP-2 levels and the plasma concentrations of markers of NO bioavailability (all P>0.05). CONCLUSIONS: There is an inverse relationship between markers of NO formation and plasma MMP-9 levels. This finding may shed some light on the possible mechanisms involved in the increased cardiovascular risk of apparently healthy subjects with low NO bioavailability or high circulating levels of pro-MMP-9.     

Genetic polymorphism of matrix metalloproteinase (MMP)-9 does not affect plasma MMP-9 activity in healthy subjects

BACKGROUND: Plasma MMP-9 levels have been shown to predict cardiovascular risk, and a functional substitution C to T at position -1562 in the promoter region of the MMP-9 gene has been associated with the severity of cardiovascular diseases. We examined the association between the C(-1562)T polymorphism and MMP-9 activity in healthy subjects. METHODS: We studied 200 healthy male white volunteers (age range: 20-55 y) who were nonsmokers and were not taking medicines. Genomic DNA was extracted and genotypes for the C(-1562)T polymorphism were determined by PCR and restriction fragment length digestion. Plasma was assayed for pro-MMP-9 and MMP-9 activities by gelatin zymography. RESULTS: The frequency of the alleles "C" and "T" were 90% and 10%, respectively. Because of the relatively low frequency of the TT genotype, we combined both TT and CT genotypes together (CT+TT group) and compared with the CC genotype group. We found no differences in pro-MM9 and MMP-9 activity levels among the genotype groups (both P>0.05). CONCLUSIONS: While the present study indicates lack of effect for the C(-1562)T polymorphism on MMP-9 activity in plasma, it is possible that the C(-1562)T polymorphism contributes to an increased cardiovascular risk under conditions of induced MMP-9 expression.     

Rapid separation of serum does not avoid artificially higher matrix metalloproteinase (MMP)-9 levels in serum versus plasma

OBJECTIVES: To examine whether the time between blood drawing and centrifugation (TBDC) affects the levels of matrix metalloproteinase (MMP)-9 and MMP-2 levels in serum and in plasma samples, and to assess whether there is correlation between MMP-9 and MMP-2 levels in serum and plasma samples. DESIGN AND METHODS: Serum and plasma samples (N=8) were separated from venous blood collected into citrate, heparin, and EDTA tubes, which were either centrifuged immediately or after 5, 10, 20, or 30 min after blood drawing. We assessed the correlation between MMP-9/MMP-2 in serum and citrate, heparin, and plasma samples (N=20), which were assayed for gelatine zymography of MMP-2 and MMP-9. RESULTS: MMPs are released by platelets or leukocytes during platelet activation or sampling process, thus leading to artificially higher MMP-9 levels in serum compared with citrate, heparin, or EDTA plasma samples, independently of TBDC. Citrate and heparin plasma samples had the lowest Pro-MMP-9 and MMP-9 levels, which correlated with each other. Pro-MMP-9 levels in serum correlated with Pro-MMP-9 levels in EDTA or citrate plasma, but not with heparin plasma. While no significant correlations were found between MMP-9 levels in serum and those found in plasma samples, the total MMP-9 levels (Pro-MMP-9+MMP-9) in serum and in plasma samples correlated with each other. No significant differences were found in pro-MMP-2 levels. CONCLUSIONS: These results suggest that the circulating levels of MMP-9 should be assessed in citrate or heparin plasma samples, but not in serum samples because of artificially higher MMP-9 levels in serum, independently of TBDC, and because they do not correlate with the MMP-9 levels in plasma samples.